Cannabinoid 1 (CB1) receptors coupled to cholinergic motorneurones inhibit neurogenic circular muscle contractility in the human colon

British Journal of Pharmacology
Nicholas M HindsScott D Smid

Abstract

The effects of cannabinoid subtype 1 (CB(1)) receptor activation were determined on smooth muscle, inhibitory and excitatory motorneuronal function in strips of human colonic longitudinal muscle (LM) and circular muscle (CM) in vitro. Electrical field stimulation (EFS; 0.5-20 Hz, 50 V) evoked a relaxation in LM and CM precontracted with a neurokinin-2 (NK-2) selective receptor agonist (beta-ala(8)-neurokinin A; 10(-6) M) in the presence of atropine (10(-6) M); this was unaltered following pretreatment with the CB(1)-receptor selective agonist arachidonyl-2-chloroethylamide (ACEA; 10(-6) M). In the presence of nitric oxide synthase blockade with N-nitro-L-arginine (10(-4) M), EFS evoked a frequency-dependent 'on-contraction' during stimulation and an 'off-contraction' following stimulus cessation. On-contractions were significantly inhibited in CM strips by pretreatment with ACEA (10(-6) M). These inhibitory effects were reversed in the presence of the CB(1) receptor-selective antagonist N-(piperidine-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (10(-7) M). ACEA did not alter LM or CM contractile responses to acetylcholine or NK-2 receptor-evoked contraction. Immunohistochemical studies reveal...Continue Reading

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